Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis.

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years. One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).

Shared and Anxiety-Specific Pediatric Psychopathology Dimensions Manifest Distributed Neural Correlates.

Background: Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis designed to model mutual dependencies between symptom dimensions and neural measures.

Altered Uncinate Fasciculus Microstructure in Childhood Anxiety Disorders in Boys But Not Girls.

Objective: Anxiety disorders are common, can result in lifelong suffering, and frequently begin before adolescence. Evidence from adults suggests that altered prefrontal-limbic connectivity is a pathophysiological feature of anxiety disorders. More specifically, in adults with anxiety disorders, decreased fractional anisotropy (FA), a measure of white matter integrity, has been observed in the uncinate fasciculus, the major tract that connects limbic and prefrontal regions.

Levels of early-childhood behavioral inhibition predict distinct neurodevelopmental pathways to pediatric anxiety.

Background: Anxiety symptoms gradually emerge during childhood and adolescence. Individual differences in behavioral inhibition (BI), an early-childhood temperament, may shape developmental paths through which these symptoms arise. Cross-sectional research suggests that level of early-childhood BI moderates associations between later anxiety symptoms and threat-related amygdala-prefrontal cortex (PFC) circuitry function.

The Integration of Functional Brain Activity from Adolescence to Adulthood.

Age-related changes in human functional neuroanatomy are poorly understood. This is partly due to the limits of interpretation of standard fMRI. These limits relate to age-related variation in noise levels in data from different subjects, and the common use of standard adult brain parcellations for developmental studies.

Neural responses to reward in childhood: relations to early behavioral inhibition and social anxiety.

Behavioral inhibition (BI) is an early temperamental profile characterized by negative reactivity to novelty, withdrawal from social situations, and increased risk for social anxiety. Previous research associated BI assessed in early childhood to striatal hypersensitivity in mid-to-late adolescence. The present study examined this association among 10 year-olds, characterized with BI at ages 24 and 36 months on measures of temperamental reactivity.

Early Childhood Behavioral Inhibition Predicts Cortical Thickness in Adulthood.

Objective: Behavioral inhibition (BI) during early childhood predicts risk for anxiety disorders and altered cognitive control in adolescence. Although BI has been linked to variation in brain function through adulthood, few studies have examined relations between early childhood BI and adult brain structure.

Method: The relation between early childhood BI and cortical thickness in adulthood was examined in a cohort of individuals followed since early childhood (N = 53, mean age 20.

Robust resting state fMRI processing for studies on typical brain development based on multi-echo EPI acquisition.

Several methodological challenges affect the study of typical brain development based on resting state blood oxygenation level dependent (BOLD) functional MRI (fMRI). One such challenge is mitigating artifacts such as those from head motion, known to be more substantial in younger subjects than older subjects. Other challenges include controlling for potential age-dependence in cerebrospinal fluid (CSF) volume affecting anatomical-functional coregistration; in vascular density affecting BOLD contrast-to-noise; and in CSF pulsation creating time series artifacts.

Alterations in amygdala functional connectivity reflect early temperament.

Behavioral inhibition (BI) is a temperament identified early in life that is associated with increased risk for anxiety disorders. Amygdala hyperresponsivity, found both in behaviorally inhibited and anxious individuals, suggests that amygdala dysfunction may represent a marker of anxiety risk. However, broader amygdala networks have not been examined in individuals with a history of childhood BI.

Role of contingency in striatal response to incentive in adolescents with anxiety.

This study examines the effect of contingency on reward function in anxiety. We define contingency as the aspect of a situation in which the outcome is determined by one's action-that is, when there is a direct link between one's action and the outcome of the action. Past findings in adolescents with anxiety or at risk for anxiety have revealed hypersensitive behavioral and neural responses to higher value rewards with correct performance.

Differential abnormalities of functional connectivity of the amygdala and hippocampus in unipolar and bipolar affective disorders.

Objective: The amygdala and hippocampus - two structures intimately associated with mood and cognition - have been reported to exhibit altered neural activity or volume in affective disorders. We hypothesized the amygdala and hippocampus would show altered and differential patterns of connectivity in patients with bipolar (BPs) and unipolar (UPs) disorder compared to healthy volunteers.

Method: Thirty BPs, 34 UPs, and 66 healthy volunteers were imaged using F-18-fluorodeoxyglucose and positron emission tomography while performing an auditory continuous performance task (CPT).

Antidepressant efficacy of high and low frequency rTMS at 110% of motor threshold versus sham stimulation over left prefrontal cortex.

Background: While the efficacy of repetitive transcranial magnetic stimulation (rTMS) at 10 Hz over the left prefrontal cortex has been repeatedly demonstrated, it is not clear that the optimal parameters for the treatment of depression have been adequately elucidated.

Objectives: We sought to assess the antidepressant effectiveness of high and low frequency at a higher intensity rTMS compared to sham in patients with moderately treatment resistant depression.

Method: The authors conducted a three-week, double-blind, randomized, sham-controlled study of 24 acutely depressed patients given either active 20 Hz (n = 8) or 1 Hz (n = 8) rTMS (at 110% of motor threshold [MT]) or sham treatments (n = 8) over the left prefrontal cortex.

Patterns of neural connectivity during an attention bias task moderate associations between early childhood temperament and internalizing symptoms in young adulthood.

Background: Biased attention to threat is found in both individuals with anxiety symptoms and children with the childhood temperament of behavioral inhibition (BI). Although perturbed fronto-amygdala function is implicated in biased attention among anxious individuals, no work has examined the neural correlates of attention biases in BI. Work in this area might clarify underlying mechanisms for anxiety in a sample at risk for internalizing disorders.

DRD4 and striatal modulation of the link between childhood behavioral inhibition and adolescent anxiety.

Behavioral inhibition (BI), a temperament characterized by vigilance to novelty, sensitivity to approach-withdrawal cues and social reticence in childhood, is associated with risk for anxiety in adolescence. Independent studies link reward hyper-responsivity to BI, adolescent anxiety and dopamine gene variants. This exploratory study extends these observations by examining the impact of DRD4 genotype and reward hyper-responsivity on the BI-anxiety link.

Developmental effects of decision-making on sensitivity to reward: an fMRI study.

Studies comparing neural correlates of reward processing across development yield inconsistent findings. This challenges theories characterizing adolescents as globally hypo- or hypersensitive to rewards. Developmental differences in reward sensitivity may fluctuate based on reward magnitude, and on whether rewards require decision-making.

Validation of a child-friendly version of the monetary incentive delay task.

The monetary incentive delay (MID) task (Knutson, 2000) is an imaging paradigm used to measure neural activity of incentive receipt anticipation. The task reliably elicits striatal activation and is commonly used with both adult and adolescent populations, but is not designed for use with children. In the current article, we present data on the newly designed 'piñata task' a child-friendly analog of the MID task.

Interregional cerebral metabolic associativity during a continuous performance task (Part II) : differential alterations in bipolar and unipolar disorders.

Unipolar and bipolar disorders have often been reported to exhibit abnormal regional brain activity in prefrontal cortex and paralimbic structures compared with healthy controls. We sought to ascertain how regions postulated to be abnormal in bipolar and unipolar disorders were functionally connected to the rest of the brain, and how this associativity differed from healthy controls. Thirty patients with bipolar disorder (BPs), 34 patients with unipolar disorder (UPs), and 66 healthy volunteers (Willis, M.

Interregional cerebral metabolic associativity during a continuous performance task (Part I): healthy adults.

One emerging hypothesis regarding psychiatric illnesses is that they arise from the dysregulation of normal circuits or neuroanatomical patterns. In order to study mood disorders within this framework, we explored normal metabolic associativity patterns in healthy volunteers as a prelude to examining the same relationships in affectively ill patients (Part II). We applied correlational analyses to regional brain activity as measured with FDG-PET during an auditory continuous performance task (CPT) in 66 healthy volunteers.

Repetitive TMS combined with exposure therapy for PTSD: a preliminary study.

Treatment for anxiety and post-traumatic stress disorder (PTSD) includes exposure therapy and medications, but some patients are refractory. Few studies of repetitive transcranial magnetic stimulation (rTMS) for anxiety or PTSD exist. In this preliminary report, rTMS was combined with exposure therapy for PTSD.

Preliminary findings of uncoupling of flow and metabolism in unipolar compared with bipolar affective illness and normal controls.

Cerebral metabolism (CMR for glucose or oxygen) and blood flow (CBF) have been reported to be closely correlated in healthy controls. Altered relationships between CMR and CBF have been reported in some brain disease states, but not others. This study examined relationships between global and regional CMRglu vs.

Bupropion and venlafaxine responders differ in pretreatment regional cerebral metabolism in unipolar depression.

Background: Pretreatment functional brain imaging was examined for never-hospitalized outpatients with unipolar depression compared with control subjects in a crossover treatment trial involving bupropion or venlafaxine monotherapy.

Methods: Patients (n = 20) with unipolar depression received baseline (medication-free) fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) scan and then at least 6 weeks of bupropion or venlafaxine monotherapy in a single-blind crossover trial. Age-matched healthy control subjects (n = 20) also received baseline FDG PET scans.

A potential cholinergic mechanism of procaine's limbic activation.

The local anesthetic procaine, when administered to humans intravenously (i.v.), yields brief intense emotional and sensory experiences, and concomitant increases in anterior paralimbic cerebral blood flow, as measured by positron emission tomography (PET).

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: II. Effects of prefrontal cortex rTMS.

Background: The changes in brain activity produced by repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) remain unclear. We examined intensity-related changes in brain activity with positron emission tomography (PET) in normal volunteers during rTMS delivered to the left PFC.

Methods: In 10 healthy volunteers, we delivered 1-Hz rTMS at randomized intensities over left PFC with a figure-eight coil.

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: I. Effects of primary motor cortex rTMS.

Background: Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity.

Methods: Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H(2)(15)O and PET.

Left prefrontal-repetitive transcranial magnetic stimulation (rTMS) and regional cerebral glucose metabolism in normal volunteers.

Repetitive transcranial magnetic stimulation (rTMS) holds promise as a probe into the pathophysiology and possible treatment of neuropsychiatric disorders. To explore its regional effects, we combined rTMS with positron emission tomography (PET). Fourteen healthy volunteers participated in a baseline 18-fluorodeoxyglucose (FDG) PET scan.